BACKGROUND:We aimed to conduct an individual patient data meta-analysis on blood neurofilament light chain (NfL) in ischemic stroke (IS) to enhance its clinical applicability. METHODS:We performed a systematic literature search of studies on blood NfL measured in adult patients within 30 days after IS onset and derived age- and BMI-adjusted Z-scores based on a previously published reference population of healthy controls. We collected clinical, radiological and biochemical parameters of IS patients and tested associations of NfL at defined timepoints after IS onset (D1: < 24 h; D2: 24-48 h; D3: 48-72 h; D4-5: 72-120 h; D6-7: 120-168 h; D8-30: > 168 h) with baseline characteristics and 3-month follow-up outcomes (modified Rankin Scale, mRS; survival). RESULTS:We included 4081 blood NfL values from 2872 participants (IS n = 1985, transient ischemic attack n = 88, healthy controls n = 799) of 18 published studies and 3 unpublished cohorts. In patients with IS, NfL Z-score progressively increased from D1 [median: 2.0 (IQR: 0.9-2.9)] to D6-7 [median: 3.5 (IQR: 3.0-3.8)], with discriminative ability being high for IS vs. controls (AUC: 0.79-0.97) and fair for IS vs. TIA (AUC: 0.64-0.80). Higher NfL Z-score at D1 was associated with greater risk of symptomatic intracranial hemorrhage (aOR = 1.33, p = 0.014) and, from D2 onwards, with larger infarct lesion volume (highest Spearman's rho: 0.795 at D6-7). NfL independently predicted a mRS > 2 (aOR = 1.31, p < 0.001) and mortality (aOR = 1.67, p < 0.001) at 3 months. CONCLUSIONS:Blood NfL level was progressively elevated after IS, could discriminate IS from healthy controls with high accuracy and had prognostic value for intra-hospital complications and 3-month clinical outcomes in IS.
Mindfulness-based interventions effectively improve mental health among healthcare professionals and foster compassionate care. However, the process of implementing mindfulness and ensuring long-term sustainability within hospital departments remains underexplored. Thus, this study aimed to identify and explore the mental models of healthcare professionals and managers that influence mindfulness implementation in hospital settings, to uncover strategies to support long-term sustainability. Guided by action research, 14 healthcare professionals and eight managers from two hospital departments were engaged in a 2-year mindfulness implementation process. Data collection consisted of four workshops followed by six focus group interviews. A thematic data analysis was conducted using the Immunity to Change model. Three mental models were identified: “Time pressure as a barrier for creating a mindful culture,” “A common understanding as essential,” and “Management support as a prerequisite.” Over the study period, these mental models evolved, with healthcare professionals describing their introduction to mindfulness as a “new way of being,” characterized by increased awareness, presence, and calmness. Psychological safety surfaced as an important factor for successful implementation, alongside the recognition that while management support is crucial, bottom-up initiatives from staff are equally important. Implementing mindfulness in hospital settings requires holistic strategies that address both structural and cognitive elements. This process calls for collaborative efforts that balance top-down support with bottom-up initiatives. Involving enthusiastic mindfulness ambassadors, sharing various strategies for integrating mindfulness into clinical practice, and recognizing the need for psychological safety are essential in promoting collective learning and enhancing implementation and sustainability.
The aim of this study was to evaluate the range and frequency of health complaints reported by residents potentially exposed to complex environmental pollution. Secondly, the aim was to provide individuals who suspected pollution-related health effects with the opportunity to have their concerns assessed by specialists in environmental medicine.This article describes the characteristics of residents reporting health complaints attributed to the pollution compared with a reference group of residents, who did not suspect that the pollution affected their health. An invitation was sent to all 10,460 adult residents in the town and surrounding areas, followed by a question on whether they suspected their health problems were related to the pollution. Among the 3,679 (35
Abstract Introduction: In RRMM, increasing rates of pt attrition and decreasing durability of responses with each line of therapy (LOT) necessitate early treatment (tx) with the most effective therapies. Immunotherapies that are widely accessible across different MM tx settings have the potential to change the trajectory of RRMM. Teclistamab (Tec), the first approved BCMA×CD3 bispecific antibody (BsAb) for heavily pretreated RRMM, provided deep, durable responses in MajesTEC-1, with improved efficacy and safety in earlier LOTs. Daratumumab (Dara), a standard-of-care (SoC) foundational CD38 targeted therapy with direct on-tumor activity, has been shown to deplete immunosuppressive T-cells and expand cytotoxic T-cells, creating an immune-permissive microenvironment for synergistic Tec-mediated killing of MM cells. MajesTEC-3 (NCT05083169) evaluates Tec-Dara vs SoC DPd/DVd in RRMM. We report initial results for this first phase 3 study of BsAb therapy in MM. Methods: Eligible pts had 1-3 prior LOTs including a PI and lenalidomide (Len; pts with 1 prior LOT must have been Len-refractory) with progressive disease (PD) on or after the last LOT. Pts with prior BCMA-directed therapy or refractory to anti-CD38 were excluded; prior anti-CD38 exposure was permitted. Pts were randomized 1:1 to Tec-Dara or DPd/DVd. The Tec-Dara group received 28-day cycles (C) of Tec (1.5 mg/kg QW in C1-2 [C1 preceded by the approved step-up dose schedule]; 3 mg/kg Q2W in C3-6; and 3 mg/kg Q4W in C7+) with Dara; steroids were not required after C1 Day 8. Tec and Dara dosing were aligned with the approved Dara schedule. DPd/DVd were administered per approved schedules. Progression-free survival (PFS) by IRC was the primary endpoint; secondary endpoints included complete response or better (≥CR), overall response, minimal residual disease (MRD) negativity (10–5; next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety. Results: 587 pts were randomized (Tec-Dara, n=291; DPd/DVd, n=296). Median (range) age was 64 (25-88) yrs, median number of prior LOTs was 2 (1-3). With 34.5-mo median follow-up, Tec-Dara significantly improved PFS vs DPd/DVd (HR, 0.17; 95% CI, 0.12-0.23; P<0.0001); mPFS was NR and 18.1 mo, and 36-mo PFS rate was 83.4% and 29.7%, respectively. PFS benefit was consistent across all prespecified and clinically relevant pt subgroups, including age ≥75 yrs, Len-refractory, high-risk cytogenetics, ≥60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposed. Significantly higher rates of ≥CR (81.8% vs 32.1%; OR, 9.56; 95% CI, 6.47-14.14), overall response (89.0% vs 75.3%; OR, 2.65; 95% CI, 1.68-4.18), and MRD-negativity (58.4% vs 17.1%; OR, 6.78; 95% CI, 4.53-10.15) were observed with Tec-Dara (P<0.0001). There were 45 deaths with Tec-Dara and 96 with DPd/DVd, primarily due to PD (4.6%; 20.3%). OS significantly favored Tec-Dara (HR, 0.46; 95% CI, 0.32-0.65; P<0.0001), including across all prespecified subgroups. The 36-mo OS rates were 83.3% and 65.0%, respectively and >90% of Tec-Dara pts alive at 6 mo were also alive at 30 mo. Median time to worsening of MM symptoms was NR with Tec-Dara vs 39.9 mo with DPd/DVd (HR, 0.50; 95% CI, 0.34-0.72; P=0.0002). At data cutoff, 49.4% of pts remained on study tx (Tec-Dara, 71.0%; DPd/DVd, 28.3%). Median tx duration was twice as long with Tec-Dara vs DPd/DVd (32.4 vs 16.1 mo). Frequency of grade 3/4 (Tec-Dara, 95.1%; DPd/DVd, 96.6%) and grade 5 (7.8%; 6.2%) treatment-emergent adverse events (TEAEs), were comparable (safety set: Tec-Dara, n=283; DPd/DVd, n=290). Serious TEAEs occurred in 70.7% Tec-Dara and 62.4% DPd/DVd pts; tx discontinuations due to TEAEs were low (4.6% vs 5.5%). Any grade infections occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd pts, respectively; grade 3/4 infections occurred in 54.1% and 43.4%. New onset grade ≥3 infections decreased over time, coinciding with transition to Q4W dosing and supported by antimicrobial and Ig prophylaxis guidance. CRS rate was 60.1% (grade 1/2: 44.2%/15.9%) and ICANS was 1.1% with Tec-Dara. Conclusion: We demonstrate the clinically remarkable and statistically significant PFS and OS benefits of Tec-Dara vs SoC triplets in RRMM, with 83.4% of Tec-Dara pts alive and progression-free at 3 yrs. Infections with Tec-Dara were well managed with established protocols. This highly effective, off-the-shelf, immunotherapy combination represents a new SoC for RRMM as early as first relapse.
Pediatric obesity is linked to multi-organ inflammation and an increased risk of cardiometabolic and steatotic liver disease. To identify circulating biomarkers of cardiometabolic risk, we performed proximity extension assay proteomics, to quantify 149 inflammation- and cardiovascular-related proteins in a cross-sectional study of 4024 children and adolescents (2377 with obesity and 1647 with normal weight). We identified protein signatures linked to obesity, dyslipidemia, insulin resistance, hyperglycemia, hypertension, and related cardiometabolic phenotypes. Using machine learning, a three-protein panel (CDCP1, FGF21, HAOX1) combined with liver enzymes improved prediction of steatotic liver disease versus liver enzymes alone (receiver operating characteristic–area under the curve (ROC–AUC) = 0.83 vs. 0.77; DeLong’s test, P < 0.05). During a 1-year non-pharmacological obesity intervention (n = 184), reductions in adiposity were associated with decreased inflammatory cytokines (including CDCP1, FGF21), which correlated with improvements in cardiometabolic risk profiles. Here we show that circulating proteomic signatures may mediate obesity-related cardiometabolic risk in youth. This study identifies protein signatures of pediatric obesity linked to cardiometabolic risk, shows treatment-related changes, and highlights a three-protein panel predictive of steatotic liver disease for early diagnosis
